Pediatrician trained at University of Michigan Medical School, University of Hawaii and University of Chicago for residencies. Spent 20 years at the Commonwealth Health Center in Saipan, CNMI, before establishing Ebert Children's later Ebert Family Clinic in Frisco, CO in 2000. Published in the Journal of High Altitude Medicine and Biology
While HAPE may be a run-of-the-mill diagnosis for providers with years of experience practicing at altitude, it can be less straightforward for those who are unfamiliar with the condition. There are currently three recognized categories of HAPE. Classic HAPE (C-HAPE) occurs when someone who resides at low altitude travels to high altitude and develops pulmonary edema. Re-entry HAPE (R-HAPE) occurs when high altitude residents travel to low altitude, then return to high altitude. High-altitude resident pulmonary edema (HARPE) occurs in high altitude residents without a change in altitude. HARPE is often brought on by an upper respiratory tract infection.
HAPE and pneumonia can have similar presentations including shortness of breath, cough, fatigue, and malaise. Patients with either condition may have decreased oxygen saturation levels and abnormal findings on chest radiography. In response to this phenomena, Dr. Chris Ebert-Santos of Ebert Family Clinic in Frisco, Colorado (9000′) and Sean Finnegan, PA-C set out to develop a scoring system to differentiate the two diagnoses. If providers could easily differentiate between pneumonia and HAPE, this would shorten the time from presentation to diagnosis and would avoid unnecessary antibiotic use.
Dr. Chris and Sean Finnegan, PA-C summarized their research findings into a scoring system named the “Frisco Score”. They analyzed data from St. Anthony Summit Medical Center and associated clinics at or above ~2,760 meters above sea level from January 1, 2018 to May 30, 2023. The study looked at patients under the age of 19 who presented with hypoxemia or other respiratory concerns and had a chest x-ray performed and oxygen saturation measured. The final case review consisted of 138 total patients with 77 diagnosed with HAPE, 38 diagnosed with pneumonia, and 23 diagnosed with concomitant HAPE and pneumonia. Variables found to have no significance included gender, age, heart rate, and temperature. Variables with significance included respiratory rate, number of days ill, oxygen saturation, and chest x-ray findings. These significant variables were used to develop the Frisco Score. They do include a disclaimer that these findings are preliminary results on a small data set. Thus, as of yet, the Frisco Score should not be used on its own to make a diagnosis, but rather should be used as a clinical tool in differentiating conditions with similar presentations.
Oxygen saturation varied greatly between patients with HAPE and those with pneumonia. Patients diagnosed with HAPE had an average oxygen saturation of 74% and those with pneumonia had an average of 92%.
Patients who were diagnosed with HAPE had a higher average respiratory rate compared to those diagnosed with pneumonia.
In patients diagnosed with HAPE, the duration of illness, or number of days ill, was shorter than those diagnosed with pneumonia.
In comparison of chest x-rays, patients with HAPE were more likely to have diffuse findings and patients with pneumonia were more likely to have focal findings.
Overall, there were no variables associated with a concomitant diagnosis of pneumonia and HAPE.
In summary, patients diagnosed with HAPE had decreased oxygen saturation, increased respiratory rate, and diffuse findings on chest x-ray; while patients diagnosed with pneumonia had a longer duration of illness and focal findings on chest x-ray. The Frisco Score takes these variables into account to help differentiate a diagnosis of HAPE in children. Dr. Chris and Sean Finnegan, PA-C are currently presenting their findings at the 8th World Congress on Mountain and Wilderness Medicine in Snowbird, Utah. They hope that in the near future, the Frisco Score will be used to facilitate the diagnosis of HAPE by providers in high altitude communities state-wide.
References
1. Ebert-Santos, C. (2017). High-Altitude Pulmonary Edema in Mountain Community Residents. High Altitude Medicine & Biology, 18 (3), 278-284. https://doi.org/10.1089/ham.2016.0100
2. Ebert-Santos, C., Finnegan, S. (2024). Differentiating Pneumonia & HAPE in Children.
It comes as no surprise that living at altitude can take some adjustment. Travelers visiting just for a quick ski trip recognize immediately, sometimes even at Denver International Airport when first arriving at Colorado’s Mile High City at 5280 feet, that the air is “thinner” than where they might have journeyed from. That thinner air we all feel is due to our altitude living at 9,075 feet (2) here in Frisco, CO. Our bodies can feel the atmospheric changes even if we do not recognize them ourselves. As a point of reference, on the rather extreme side, the “death zone” that comes to mind when thinking of the behemoth Mount Everest, is any elevation of 26,247 feet and above (3), a zone we might not be as familiar with is the deterioration zone which begins at a mere 15,000 feet (3). In this zone, the symptoms are variable, but common manifestations are lethargy, weight loss, poor appetite, and irritability (4). Altitude experts identify 8,000 feet as the elevation where symptoms such as headaches and pulmonary edema are more likely to manifest. The good and bad effects of altitude are proportional to the elevation and variable between individuals. For all of you ‘fourteener’ fanatics out there, including myself, this comes as a reminder that we are closer than we think to detrimental elevation in our atmosphere. With this frame of reference fresh in our minds, let us take a closer look at how living in at the elevation of Frisco, Colorado at 9000 feet or the neighboring towns can affect our health.
Mountain residents who have blood tests done commonly see “red flags” next to some lab values. In particular, the complete blood count, commonly referred to as CBC. To most of us, those red flags are an alarming indicator that something must be terribly awry but au contraire, there is an explanation why we need not worry. For those of us living at altitude, there is a reduced atmospheric pressure, so although the fraction of oxygen in the air is still 21%, the molecules are further apart. Fewer oxygen molecules enter our lungs and bloodstream delivering less oxygen to our tissues(5). Remember now, we are not living on top of Mount Everest, so we are not in any danger, because our bodies are doing behind-the-scenes work for us! Our bodies are adapting by increasing the amount of red blood cells, which carry oxygen in our blood, throughout our bodies so that every organ is being supplied with the good stuff! This is exactly why athletes come here to train, to get their bodies to produce more red blood cells so they can perform at their absolute best. After three months of life in the mountains, nearly everyone has elevated red blood cells, hemoglobin, hematocrit, and red cell indices such as the MCV, (mean corpuscular volume), MCHC (mean corpuscular hemoglobin content) and MCH (mean corpuscular hemoglobin). A “normal” hemoglobin in a man who lived for years in the mountains was a signal to his doctor that the patient was anemic and in fact turned out to have colon cancer.
A more immediate response to the low oxygen environment at altitude is an increase in respiratory rate. In an interview with physician experts on altitude Dr. Elizabeth Winfield and Dr. Erik Swenson on May 30, 2023, both think this is the reason there is often a red flag for the carbon dioxide (CO2) as low, usually 17 to 19 with 20 being normal. Because this affects the acid base balance, the serum chloride ( Cl) may be slightly elevated, 107 to 108 instead of 106. Dr. Winfield also explains to her patients that fasting for labs may cause mild dehydration leading to a slightly higher BUN, blood urea nitrogen, a marker of kidney function. Another physiological response to altitude is a lower plasma volume, which may cause slight elevation in the serum protein and albumin.
So when you doctor calls you and tells you your labs are normal, ask them to drill down and explain the red flags. If you find out something new, please put a comment on our blog and share with the world! Few health care providers really understand all the changes in the human body living in hypobaric hypoxic (low pressure, low oxygen) environments.
3. Lankford, H. V. (2021). The death zone: Lessons from history. Wilderness & Environmental Medicine, 32(1), pp. 114-120. https://doi.org/10.1016/j.wem.2020.09.002.
4. West, J. C. (2013). Case law update. Legal liability in emergency medicine and risk management considerations. Journal of healthcare risk management: the journal of the American Society for Healthcare Risk Management, 33(1), pp. 53-60.
5. Cabrales, P., Govender, K. and Williams, A.T. (2020), What determines blood viscosity at the highest city in the world?. J Physiol, 598: 3817-3818. https://doi.org/10.1113/JP280206
Often, at high altitude we hear complaints of gas pain and increased flatus in our infant population. Parents often wonder, are we doing something wrong? Is my child reacting to breastmilk, or showing an intolerance to certain foods? Actually there is another explanation for increased flatus and gas pain in the high-altitude region of Colorado.
The term HAFE was coined by Dr. Paul Auerbach and Dr. York Miller and published in the Western Journal of Medicine in 1981. Their discovery began In the summer of 1980, when the two doctors were hiking in the San Juan Mountains of Colorado on a quest to summit three 14ers. During their ascent they noticed that something didn’t smell right! As the pair continued to emit noxious fumes, they began to put their scientific brains to work and discovered HAFE. The symptoms include an increase in frequency and volume of flatus, or in other terms an increase in toots! We all have familiarity in watching our bag of potato chips blow up when reaching altitude or our water bottle expanding as we head into the mountains. This reaction is due to a decrease in barometric pressure. Based on Boyle’s law, decreased barometric pressure causes the intestinal gas volume to expand, thus causing HAFE (Skinner & Rawal, 2019).
To my surprise, a gas bubble the size of a walnut in Denver, Colorado (5280 ft) would be the size of a grapefruit in the mountain region of Summit County, CO (8000+ ft)! Trapped gas is known to lead to discomfort and pain. The use of simethicone may have merit in mitigating the effects of HAFE. Simethicone works by changing the surface tension of gas bubbles, allowing easier elimination of gas. This medication, while benign, can be found over the counter and does not appear to be absorbed by the GI tract (Ingold, C. J., & Akhondi, H., 2022).
While this phenomenon may not be as debilitating as high-altitude pulmonary edema (HAPE), it deserves recognition, as it can cause a significant inconvenience and discomfort to those it inflicts. As the Radiolab podcast explained in their episode The Flight Before Christmas , expelled gas in a plane or car when driving up to the mountains can be embarrassing. While HAFE can be inconvenient, it is a benign condition and a matter of pressure changes rather than a disease or pathological process. We would love to talk more about HAFE at Ebert Family Clinic if you have any questions or concerns!
A bald eagle flies toward its nest atop a bare lodgepole pine.
As always, stay happy, safe, and healthy 😊
Taylor Hollingsworth is finishing her final semester as a family nurse practitioner (FNP) student at Georgetown University. Originally from the east coast, Taylor plans to start her FNP career in North Carolina close to family. She has a passion for pediatric and family wellness and has worked as a pediatric intensive care unit nurse for 6 years! In her free time, Taylor loves to hike, fly fish, run, and spend time with her fiancé Logan.
References
Auerbach, P. & Miller, Y. (1981). High altitude flatus expulsion. The Western Journal of Medicine, 134(2), 173-174.
Health care providers and people who live at altitude often believe that living in the mountains protects from altitude related illness. And yes, there are many ways the body acclimatizes over days, weeks, months, and years, as addressed in previous blog entries. However, as a physician who has practiced in high altitude communities for over 20 years, my personal observation that we are still at risk for serious complications was reenforced by a recent publication by Dr. Santiago Ucrós at the Universidad de los Andes School of Medicine in Santa Fe de Bogotá, Colombia. His article, High altitude pulmonary edema in children: a systemic review, was published in the journal Pediatric Pulmonology in August 2022. He included 35 studies reporting 210 cases, ages 0-18 years, from 12 countries.
Consistent with our experience in Colorado, the most common ages were 6-10 years and second most common 11-15 years. I have not seen or read any reports of adults affected. Cases included two deaths, which I have also seen here.
I receive reports on any of my patients seen in urgent or emergency care. Accidents, avalanches, and suicide attempts are what we think of first needing emergency care in the mountains. However, the most common critical condition is Reentry HAPE. This is a form of pulmonary edema that can occur in children who are returning from a trip to lower altitude. Think visiting Grandma during school break. Dr. Ucrós’ review also confirms that all presentations of HAPE (classic, as in visitors, reentry, and HARPE, resident children with no history of recent travel) are more common in males by a 2.6 to 1 ratio. Analysis of time spent at lower altitude before the episode showed a range of 1.6 to 30 days with a mean of 11.3 days. Mean time between arrival and onset of symptoms for all types of HAPE was 16.7 hours. The minimum altitude change reported in a HAPE case was 520 meters (1700 feet), which is the difference between Frisco, CO (Summit County) and Kremmling, CO (Grand County, the next county over). A new form of HAPE in high altitude residents who travel to higher altitude was designated HL-HAPE in this review. A case report will be featured in an upcoming blog interview with a Summit County resident who traveled to Mt. Kilimanjaro.
As with all cases of HAPE, the victims develop a cough, sound congested as the fluid builds up in their lungs, have fatigue, exercise intolerance, with rapid onset over hours of exposure to altitude, usually above 8000 ft or 2500m. Oxygen saturations in this paper ranged from 55 to 79%. My patients have been as low at 39% in the emergency room. Children presenting earlier or with milder cases come to the office with oxygen saturations in the 80’s. An underlying infection such as a cold or influenza is nearly always present and considered a contributing factor. Everyone living or visiting altitude should have an inexpensive pulse oximeter which can measure oxygen on a finger. Access to oxygen and immediate treatment for values under 89 can be life-saving.
The recurrence rate for all types of HAPE is about 20%. Most children never have another episode, but some have multiple. Preventive measures include slower return to altitude, such as a night in Denver, acetazolamide prescription taken two days before and two days after, and using oxygen for 24-48 hours on arrival. Most families learn to anticipate, prevent, or treat early and don’t need to see a health care provider after the first episode.
On January 26, 2023 I met with Dr. Ucrós and other high altitude scientists including Dr. Christina Eichstaedt, genetics expert at the University of Heidelberg in Germany, Dr. Deborah Liptzen, pediatric pulmonologist, and Dr. Dunbar Ivy, pediatric cardiologist, both from the University of Colorado and Children’s Hospital of Colorado, and Jose Antonio Castro-Rodríguez MD, PhD from the Pontifica Universidad Católica in Santiago de Chile.
We discussed possible genetic susceptibility to HAPE and hypoxia in newborns at altitude with plans to conduct studies in Bogotá and Summit County, Colorado.
Louie was excited to get out on the slopes after spending Thanksgiving with family in Vermont. He got tired early and felt his breathing was harder than usual, leaving early to go home and rest. As a competitive skier he thought that was strange. But he was getting over a cold. He could not have imagined that in 24 hours he would be in the emergency room, fighting for his life.
Louie experienced a dangerous condition, set off by altitude, and inflammation from his “cold”, that caused his lungs to fill with fluid. His oxygen saturation was 54 % instead of the normal 92, he had been vomiting and feeling very weak and short of breath. His blood tests showed dehydration, hypoxemia and acute kidney injury. His chest x-ray looked like a snowstorm. He was transferred to Children’s Hospital in Denver and admitted to the intensive care unit.
The diagnosis of Re-entry HAPE was confirmed by echocardiogram showing increased pressures in his lungs. He improved rapidly with oxygen and low altitude.
Re-entry HAPE is not rare, affecting several Summit County children every year. Many do not come to medical attention because after their first episode parents carefully monitor their oxygen and have a concentrator available in their home when they return from travel.
Medical providers may not be aware of this risk, expecting that children living at altitude are acclimatized. (See previous blog entry on Acclimatization vs. Adaptation, April 17, 2019) Re-entry HAPE seems to occur mostly in children between the ages of 4 and 15. Inflammation, such as a viral respiratory infection, seems to play a role. Trauma may also predispose a returning resident to Re-entry HAPE, as described in our blog post from February 5, 2018, Re-entry HAPE in High Altitude Residents.
Louie agreed to share his story on our blog to help educate medical personnel and families living in the mountains about this dangerous condition. Further research will help define who is at risk. The University of Heidelberg recently published an article on the genetics of pulmonary hypertension (HARPE is the New HAPE) and is interested in testing families here who have had more than one person affected by HAPE.
It took ten years for me to convince high altitude experts that children living in the mountains get high altitude pulmonary edema (HAPE) without leaving home. My observations were published in 2017 in the Journal of High Altitude Medicine and Biology,
High-Altitude Pulmonary Edema in Mountain Community Residents
This week Dr. Jose A Castro-Rodriguez MD PhD ATSF discussed HAPE in children at the 8th World Hypoxia conference in La Paz including the now renamed high altitude resident pulmonary edema (HARPE) in his presentation.
Dr. Castro-Rodriguez emphasized the importance of recognizing the three forms of HAPE, including reentry HAPE when children return to the mountains from vacation, since these can be life threatening.
My work has been cited in articles by pulmonologists Deborah Liptzin and Dunbar Ivy from Children’s Hospital of Colorado and geneticist Christine Eichstaedt and her team at the University of Heidelberg.
At Ebert Family Clinic we give every patient/family a free pulse oximeter. The ability to measure the oxygen saturation of anyone with cough, congestion, or fatigue can facilitate early treatment with oxygen and prevent visits to the emergency room, hospital and intensive care unit.
I recently received first prize for a poster presentation on HARPE at the fall Colorado Medical Society meeting, and second prize for a poster on Trauma and HAPE.
For more information about HAPE, HARPE and Trauma-related HAPE, see previous blog entries.
References
Ebert-Santos C. High-Altitude Pulmonary Edema in Mountain Community Residents. High Alt Med Biol. 2017 Sep;18(3):278-284. doi: 10.1089/ham.2016.0100. Epub 2017 Aug 28. PMID: 28846035.
Giesenhagen AM, Ivy DD, Brinton JT, Meier MR, Weinman JP, Liptzin DR. High Altitude Pulmonary Edema in Children: A Single Referral Center Evaluation. J Pediatr. 2019 Jul;210:106-111. doi: 10.1016/j.jpeds.2019.02.028. Epub 2019 Apr 17. PMID: 31005280; PMCID: PMC6592742.
Liptzin DR, Abman SH, Giesenhagen A, Ivy DD. An Approach to Children with Pulmonary Edema at High Altitude. High Alt Med Biol. 2018 Mar;19(1):91-98. doi: 10.1089/ham.2017.0096. Epub 2018 Feb 22. PMID: 29470103; PMCID: PMC5905943.
Eichstaedt CA, Mairbäurl H, Song J, Benjamin N, Fischer C, Dehnert C, Schommer K, Berger MM, Bärtsch P, Grünig E, Hinderhofer K. Genetic Predisposition to High-Altitude Pulmonary Edema. High Alt Med Biol. 2020 Mar;21(1):28-36. doi: 10.1089/ham.2019.0083. Epub 2020 Jan 23. PMID: 31976756.
The Nobel prizes are announced this month. Alfred Nobel invented dynamite in 1866. Within 30 years, Nobel made a large fortune from his invention. He demonstrated his passion for literature and science by creating a yearly prize to discoveries most beneficial to humankind. The five prize categories include physics, chemistry, medicine (physiology), literature and peace. The Nobel prize nominations are made by university professors, national assemblies, state governments, and international courts. The prize is awarded yearly to individuals who have discovered a new paradigm or a paradigm shift within their field. The prize recipients are declared on the first Monday of October of every year and the award is presented by the Nobel assembly on November 10th, the anniversary of Alfred Nobel’s death. The Nobel prize consists of a gold medal, a diploma of recognition of achievement, and a cash prize in the amount of $1 million U.S. dollars.
There is no limit to the number of nominations that can be made or the number of times that an individual can be nominated. There were 400 candidates nominated in the field of medicine in 2019, all of which inspired, challenged, and demonstrated greatness in their field. In 2019 the Nobel Prize in Medicine honored three scientists for their discovery of the human body’s ability to adapt to low oxygen environments.
Hypoxia is a state of which oxygen supply is insufficient for normal life functions, experienced by the human body at high altitude. Tissues and cells require a range of oxygen in order to survive. Oxygen is required by mitochondria, in all cells, to convert food into useable energy. “Otto Warburg, the recipient of the 1931 Nobel Prize in Physiology or Medicine, revealed that this conversion is an enzymatic process.” At low oxygen environments, as experienced at high altitude, the body must adapt in order to maintain basic cellular function. There are several mechanisms in the human body that increase oxygen concentration including breathing rate, regulated by the carotid body, increased heart rate, stimulated by the vagus nerve, and increased production of red blood cells (RBCs) through the bone marrow, regulated by the kidney.
The carotid body is a chemoreceptor near the carotid artery that detects oxygen, carbon dioxide and pH levels in the blood. At low oxygen, the carotid body relays an afferent (ingoing) signal to the the brain via the glossopharyngeal nerve. The medullary center in the brain then sends an efferent (outgoing) signal that increases the respiratory rate to maximize oxygen delivery to the brain. The carotid sinus is a baroreceptor near the aorta of the heart which senses changes in pressure. As pressure increases in the atmosphere, experienced at high altitude, the carotid sinus sends a signal along the vagus nerve to the brain which then increases the heart rate. “The 1938 Nobel Prize in Physiology or Medicine was awarded to Corneille Heymans for discoveries showing how blood oxygen sensing via the carotid body controls our respiratory rate by communicating directly with the brain.”
At low oxygen environments, the kidney increases production of erythropoietin, which stimulates RBC generation in the bone marrow, called erythropoiesis, resulting in higher oxygen delivery to the brain and skeletal muscles needed at high altitude. Erythropoiesis was discovered in the early 20th century, however oxygen’s role in the process was not completely understood. The cell’s ability to sense and adapt to oxygen availability was discovered and explained by three scientists, William G. Kaelin Jr., Sir Peter J. Ratcliffe and Gregg L. Semenza.
2019 Nobel Prize, Physiology:
Thanks to the work of Dr. Gregg L. Semenza and Sir Peter J. Ratcliffe, we now understand that the oxygen sensing mechanism that stimulates erythropoieten is present in all tissues, not just the kidney. Semenza conducted research on liver cells using gene-modified mice and found that a specific protein binds to an individual gene (the EPO gene), dependent upon oxygen availability. Semenza named the binding protein the Hypoxia-Inducible-Factor (HIF). The HIF protein was found to compose two transcription factors, HIF-1alpha and ARNT. In 1995, Semenza published his findings of the HIF protein. His work explained that when the body is at high oxygen environments, there is very little HIF-1alpha present within cells. At high oxygen availability, HIF-1alpha is rapidly degraded by a proteasome within cells. The degradation is signaled by a protein called ubiquitin which binds to HIF-1alpha at high oxygen, flagging HIF-1alpha for degradation by the proteasome. This process was recognized by the 2004 Nobel Prize in Chemistry, Aaron Ciechanover, Avram Hershko and Irwin Rose.
The mechanism by which ubiquitin binds, causing the degradation of HIF-1alpha at high oxygen environments was explained by the work of William Kaelin, Jr. who conducted research on von Hippel-Lidau’s (VHL) disease. The VHL gene mutation causes an increased risk of cancer. Kaelin showed that the VHL gene encodes a protein that prevents the onset of cancer and was involved in controlling responses to hypoxia. VHL is part of a complex that labels proteins with ubiquitin. Ratcliffe discovered the physical interaction of the VHL gene with HIF-1alpha, causing degradation of the HIF-1alpha at normal oxygen levels.
At hypoxic environments, HIF-1α is protected from degradation and accumulates in the nucleus, where it associates with ARNT and binds to specific DNA sequences (HRE) in hypoxia-regulated genes (1). At normal oxygen levels, HIF-1α is rapidly degraded by the proteasome (2). Oxygen regulates the degradation process by the addition of hydroxyl groups (OH) to HIF-1α (3). The VHL protein can then recognize and form a complex with HIF-1α leading to its degradation in an oxygen-dependent manner (4).
At hypoxic environments, HIF-1α is protected from degradation and accumulates in the nucleus, where it associates with ARNT and binds to specific DNA sequences (HRE) in hypoxia-regulated genes (1). At normal oxygen levels, HIF-1α is rapidly degraded by the proteasome (2). Oxygen regulates the degradation process by the addition of hydroxyl groups (OH) to HIF-1α (3). The VHL protein can then recognize and form a complex with HIF-1α leading to its degradation in an oxygen-dependent manner (4).
Kaelin and Ratcliffe’s research identified how oxygen levels regulate the interaction between VHL and HIF-1alpha. Their work demonstrated that at normal oxygen levels, hydroxyl groups are added to specific positions within HIF-1alpha, causing modification of the protein and allowing VHL to recognize and bind to HIF-1alpha, leading to degradation of the protein complex. At high altitude, cells produce a greater amount of the HIF-1alpha protein which binds to the EPO gene, up-regulating the production of erythropoietin hormone, stimulating RBC production. Together, Semenza, Kaelin, and Ratcliffe explained the oxygen sensing mechanism.
Have you ever wondered why a bag of chips will swell almost to the point of bursting when you travel from a lower elevation? As the altitude increases the barometric pressure decreases. The difference between the high pressure inside the bag and the low pressure outside causes the bag to swell (and sometimes burst) to reach equilibrium with the surrounding environment.
The same concept applies to our biological tissue, including our eyes. Luckily there is not normally gas in our eyes, but there are procedures where air bubbles are injected into the eye, such as a vitrectomy: part of the vitreous humor of the eye is replaced with air so that a nearby site has the chance to heal. Common indications include a retinal detachment, macular hole or removal of scar tissue. It’s important to remain at the elevation your ophthalmologist or optometrist indicates because you don’t want your eye to suffer the same fate as a bag of chips!
This was one of many interesting things I learned while speaking with D. Paul Cook, OD and his wife and practice manager Karen Cook at Summit Eye Center on Main Street in beautiful Frisco, CO. The following is my interview with Dr. Cook, Karen Cook, and my preceptor Christine Ebert-Santos, MD, MPS.
How many years have you been practicing optometry in Frisco, CO?
I don’t recall the exact year, but I remember it was the year the Broncos lost the Superbowl.
Dr. Paul Cook at the entrance of Summit Eye Center.
I did a little research and this must have been either the 1986 or 1987 season, as the Broncos lost both of those Superbowls. Fortunately, those Superbowl losses were not a bad omen as Dr. Cook has successfully served the Frisco area every year since.
What conditions do you see commonly here at altitude?
One thing I see commonly here is recurrent corneal abrasions. The classic patient lives at a lower altitude and previously had a corneal abrasion. They received treatment but the abrasion site never completely heals. After arrival in the high country where it’s extremely dry that abrasion site dries up and becomes inflamed.
Usually what I do is give a bandage contact lens to cover up that recurrent corneal abrasion, which usually works, but if it’s extremely painful, we can use amniotic membrane, which is expensive. But it is effective.
The cornea is the outermost layer of the eye (if you don’t count the tear film). A corneal abrasion occurs when any foreign object scrapes the corneal surface. Symptoms include a foreign body sensation, pain, clear discharge, blurry vision and sensitivity to light. A corneal abrasion needs a healthy, moist environment in order to heal. You can see how the dryness that comes along with altitude could lead to a recurrent corneal abrasion.
I also see a fair amount of snow blindness, usually in the spring though.
I suppose it has to do with the sun being higher in the sky and people being out and about hiking. When people are out skiing in the cold winter they wear their goggles, but if it’s spring time and somebody’s hiking they might forget their glasses.
Snow blindness is only one potential cause of a disease called photokeratitis. Other causes are staring at the sun, looking at an arc welder, or catching too many refracted UV rays from surfaces such as sun, water, ice and snow. The pathophysiology for each disease is the same: too many UV rays are focused onto the cornea at one time which causes damage. Symptoms include pain, redness, blurriness, sensitivity to bright light, headache, and occasionally temporary vision loss. Treatment for photokeratitis caused by snow blindness is supportive, but the most important thing is resting your eyes. Try to get into a dark room and avoid anything that makes your eyes uncomfortable. In a few days your cornea should heal.
Prevention is straightforward: wear sunglasses or ski goggles with adequate sun protection.
Are cataracts a more common condition at altitude?
Oh yes, because of sun exposure and our aging population here. The people of Summit County are so active, which increases their exposure to the damaging rays of the sun. We’re also treating cataracts so much sooner than we used to, so that’s part of what makes it more common.
Do you have any recommendations for healthy aging at altitude as it relates to the eyes?
Karen: Getting your annual eye exam. We always tell patients there are a lot of things we can do to preserve your vision, there’s almost nothing we can do to give it back to you.
So if you live in Frisco, CO and don’t have an optometrist, make sure to see Dr. Paul Cook!
Is blurry vision a common malady in patients that have recently received a LASIK procedure and then ascended to higher elevations?
I have not seen that with LASIK. About 30 years ago though there was a procedure called Radial Keratotomy (RK) that involved a surgeon making radial cuts on the cornea in order to correct nearsightedness. Those patients used to require one pair of glasses for where they lived at lower elevation and one pair of glasses at higher elevation. It’s not a procedure commonly done nowadays but patients that had RK roughly 30 years ago may have that problem.
LASIK stands for Laser Assisted In Situ Keratomileusis. It essentially means that the surgeon will use a laser to reshape the cornea so that the light refracting through it will be appropriately concentrated on the retina. LASIK is faster, cheaper, safer and more effective than RK. It has largely usurped RK for surgical treatment of nearsightedness or farsightedness.
What are some interesting cases you have seen over your years of practice?
I treated a patient that traveled from the Midwest and had a genetic condition called retinitis pigmentosa. Clinically that means the patient had limited peripheral vision at baseline. He and his wife decided to hike the Colorado Trail. Unfortunately during the hike he developed blurred vision and ended up coming into my office. Turns out he had macular edema and I referred him to an ophthalmologist down in Denver because the altitude was probably the cause of his macular swelling. I called him a few weeks later and his vision had returned to normal.
Another patient came into the office because his wife had noticed growths on his iris that turned out to be nevi (colloquially known as moles when they’re on the skin). So I dilated his eyes and noticed growths on his retina. I referred him down to oncology in Denver for a biopsy and it turned out to be melanoma. I think they’re closely monitoring that melanoma at this point. It’s uncommon to see cancers of the eye but I see them once every few years.
Dr. Cook performing an eye exam on me.
For my last question, do you have any general recommendations for residents or visitors?
Wear sunglasses, eat your vegetables, eat your fish at least two times per week, keep your cholesterol in check, keep your sugars in check, take breaks from looking at the computer, don’t sleep in your contacts, and see your optometrist once per year.
Seth Selby is a second-year physician assistant student at Des Moines University. He was raised in Eaton, CO and attended Colorado State University with a bachelor’s degree in Health and Exercise Science. Prior to PA school, Seth worked for 3 years as a Cardiovascular Technician at Boulder Community Hospital. In his spare time Seth loves backpacking, hunting, fishing, skiing and astronomy.
My name is Austin Ethridge, I am a physician assistant student from Red Rocks Community College PA program who has been fortunate enough to have completed my pediatric rotation with Dr. Chris in Frisco, Colorado, this month. Dr. Chris has extensive experience providing care to the pediatric residents of Summit County, having established her practice here in 2000, following 20 years as a pediatrician on Saipan, in the Northern Mariana Islands, southeast of Japan. She has a unique perspective on high altitude health, having transitioned from sea level to the 8000′ and above elevations unique to Summit County. Since moving here, she has been advocating for more in-depth medical research regarding the needs specific to these high-altitude communities. We are here in her office today at the Ebert Family Clinic to discuss neonatal oxygen use in Summit County.
Dr. Chris, based on your experience, why do neonates need oxygen at a higher elevation? Is it because they need to acclimate?
Yes, that’s basically it, and smaller lung size at birth.
Yes, that’s what I read. Basically, the maternal physiology compensates for the higher altitude. When the infant is born, their lung size and physiology need to catch up to the altitude.
Based on your practice, when do you place neonates on oxygen?
Usually at 89% or below, but you see, that’s just it. Many parents ask why their children need to be on oxygen when neither themselves nor their siblings were on oxygen. One of the primary reasons that this has become more of an issue is the less invasive methods of measuring oxygen saturation in the blood. Before the 1990s, the only time to measure oxygen saturation in a newborn was if a concern for illness or pulmonary problems existed, which was completed by obtaining an arterial blood gas, a very invasive procedure. Do you know at what oxygen saturation level we begin to detect cyanosis in neonates?
Around75%, which means before the pulse oximeter used today, we had no idea if the infant’s oxygen saturation was in the 80s! Now that we have the pulse oximeter, we have access to so much more information. And this is why it is essential to determine the normal oxygen levels for these infants at higher elevations.
Does this include cyanosis or blue discoloration of the hands and feet, or is it just central as in the face and chest?
The blue discoloration of legs and arms do not count; this is very common and not concerning, only the discoloration of the trunk and face.
Yes, based on the articles that I have been reading while I have been here, there are not many studies that reflect normal oxygen saturation in neonates at a higher elevation. Most of the articles that I did find determined that newborn oxygen saturation is lower at elevations of around 6000’, with average values within the range of 89-96% SpO2 compared to greater than 97% at sea level. However, there could be a significant difference between 9000’-10000’ feet and the 6000’ in these studies.1-3
That is exactly right, and that is why I want to do a study here in Summit County to determine the average oxygen saturation at these altitudes.
On average, how many newborns do you place on oxygen in Summit County?
About 40% of newborns are placed on oxygen due to low oxygen levels at birth, and I would say that less than 5% will still need oxygen after their two-week visit; however, this rate may be higher in those that live at elevations of 10,000′ or greater. In general, studies have observed that the lowest oxygen levels tend to occur around the 4th day of life and then improve from this point onward. What is the main complication that we are worried about in infants that have low oxygen levels?
Pulmonary hypertension. At birth, when the fetal circulation is shunted back through the lungs, the pulmonary pressure decreases to allow this to happen. If the oxygen levels are too low, the vessels in the lungs may not dilate enough, and this could lead to elevated pulmonary pressures. I read an interesting study that found increased pulmonary pressures in Tibet children as measured by ECHO cardiogram until the age of 14. These pressures were noted to increase with increasing elevation but to decrease with increasing age. Generally, by the age of 14, the pulmonary pressures had normalized; the authors considered this to be a normal physiological response. However, it is worth noting that these children in the study came from generations of individuals that have always lived at these altitudes.4-5
That is correct. That is the difference between adaptation and acclimatization. Many of the children that live up here are acclimatized, meaning that their bodies have adapted on a physiological level, but their genetics remain the same. However, adaptation is observed in many families that have lived at high elevations for generations; in these instances, the changes have occurred at the genetic level.
That makes sense; so the data from some of those studies may not directly apply to the population here.
That is correct. Are we worried about brain damage in this setting of low blood oxygen levels?
No, I do not think so.
We are not! In fact, as an example of this: when I was in Saipan, there was a child that had a cyanotic, congenital heart defect that was unable to be repaired for social reasons. This child always appeared blue, and his oxygen saturation would have been very low. He did just fine in terms of development and progress in academics. There were no signs of developmental delay or any other neurological problems at all.
Are there any resources you recommend for parents whose newborn may need to be on oxygen?
Are there any red flags or signs that the newborns’ oxygen may not be high enough when they are sent home? Is there anything parents should look out for? I know that you mentioned the oxygen level needs to be as low as 75% before there are any signs of concerning central cyanosis.
No, there really are no clinical signs. A company called Owlet produces a sock for the newborn’s foot that monitors oxygen saturation. I am not sure how accurate this is, but if the parents really want to do something to monitor the oxygen level, this could be a way to do so. It is pretty expensive. On an aside, we are currently in communication with this company regarding future opportunities to conduct research using their product with regards to newborn oxygen saturation at higher elevations, so stay tuned for more developments on this topic.
Are there any risks to starting the infant on oxygen?
No, not at the level that these newborns are sent home on. In premature infants, there is a risk associated with oxygen therapy for eye and lung disease. However, these premature infants are placed on very high flow rates and positive pressures. The damage is actually caused by the pressures of the oxygen being too high. This is not the case for the newborns that we place on oxygen.
Are there any risks to infants or children growing up at high altitude?
Yes, there is some evidence of a very slight increased risk of pulmonary hypertension, but this is very rare.
Thank you so much for taking the time to discuss this, Dr. Chris!
References
Ravert P, Detwiler TL, Dickinson JK. Mean oxygen saturation in well neonates at altitudes between 4498 and 8150 feet. Adv Neonatal Care. 2011 Dec;11(6):412-7. doi: 10.1097/ANC.0b013e3182389348. Erratum in: Adv Neonatal Care. 2012 Feb;12(1):27. PMID: 22123474.
Morgan MC, Maina B, Waiyego M, Mutinda C, Aluvaala J, Maina M, English M. Oxygen saturation ranges for healthy newborns within 24 hours at 1800 m. Arch Dis Child Fetal Neonatal Ed. 2017 May;102(3):F266-F268. doi: 10.1136/archdischild-2016-311813. Epub 2017 Feb 2. PMID: 28154110; PMCID: PMC5474098.
Bakr AF & Habib HS, Normal Values of Pulse Oximetry in Natewborns at High Altitude. Journal of Tropical Pediatrics 2005; 51(3) 170-173.
Qi HY, Ma RY, Jiang LX, et al. Anatomical and hemodynamic evaluations of the heart and pulmonary arterial pressure in healthy children residing at high altitude in China. Int J Cardiol Heart Vasc. 2014;7:158-164. Published 2014 Nov 12. doi:10.1016/j.ijcha.2014.10.015
Remien K, Majmundar SH. Physiology, Fetal Circulation. [Updated 2020 Aug 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539710/
Thilo EH, Park-Moore B, Berman ER, Carson BS. Oxygen Saturation by Pulse Oximetry in Healthy Infants at an Altitude of 1610 m (5280 ft): What Is Normal? Am J Dis Child. 1991;145(10):1137–1140. doi:10.1001/archpedi.1991.02160100069025
Austin Ethridge is a second-year physician assistant student at the Red Rocks Community College Physician Assistant Program. Originally from the Colorado front range, Austin attended the University of Northern Colorado where he obtained both a bachelors and masters degree in chemistry prior to attending PA school. In his free time, Austin enjoys spending time with his friends and family, reading, and cycling.
Last week we were privileged to have a Zoom discussion with two high altitude experts from the Instituto Pulmonar Y Patologia de la Altura (IPPA) founded in La Paz, Bolivia in 1970. Dr Gustavo Zubieta-Calleja and Dr. Natalia Zubieta-DeUrioste answered our questions about their recently published article, Does the Pathogenesis of SAR-CoV-2 Virus Decrease at High Altitude?. They and the seven coauthors presented data comparing COVID cases in high altitude areas of China, Bolivia and Ecuador showing a marked reduction in numbers compared to low altitude areas in the same countries, with dramatic, colorful topographic maps.
Drs. Zubieta-Calleja and Zubieta-DeUrioste and their colleagues theorized four reasons why altitudes above 2500 m could reduce the severity of the corona virus. (Note: Frisco, CO is at 2800 m, Vail 2500 m). As described in their previous paper published in March, the intense UV radiation at altitude as well as the dry environment likely reduce the viability of the virus in the air and on surfaces.
Dr. Zubieta-Calleja on a Zoom chat with Dr. Chris explaining a chart comparing UV exposure in La Paz, Bolivia (top line) and Copenhagen, Denmark (bottom line).
Dr. Chris with Dr. Gustavo Zubieta-Calleja and other altitude experts from the Hypoxia Conference in La Paz on the Camino Chacaltaya, which reaches an elevation of 17,785’/5421 m.
The low barometric pressure causes air particles to be spaced more widely, which would also decrease the viral particles inspired with each breath, reducing the severity and frequency of infections.
Furthermore, residents accustomed to chronic hypoxia may express reduced levels of angiotensin converting enzyme 2 (ACE2) in their lungs and other tissues. This enzyme has been found to be the entry path for the corona virus into cells where it replicates. Finally, the normal adaptation and acclimatization of populations with prolonged residence above 2500 meters may reduce the severity of the disease in individuals, and reduce mortality. This includes increased ventilation, improved arterial oxygen transport, and higher tissue oxygenation mediated by increased red blood cells produced under the influence of erythropoietin, which could be explored as a possible therapy.
Dr. Zubieta-Calleja with statistics reflecting the number of COVID-19 infections at different elevations in Bolivia. Note the most infections occur at a lower elevation.
As we stated in our interview quoted in the Summit Daily News March 17th, none of these factors can be relied upon to protect every individual. Therefore it is important to continue frequent hand washing, wearing masks, social distancing, and avoid touching your face.
